Donepezil-responsive alcohol-related prolonged delirium.
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Aged↗
Biomedical subjects
Toshiya Inada
Publications and source records attributed to Toshiya Inada.
Extrapyramidal symptom profiles assessed with the Drug-Induced Extrapyramidal Symptom Scale: comparison with Western scales in the clinical double-blind studies of schizophrenic patients treated with either olanzapine or haloperidol.
The superiority of olanzapine to haloperidol with respect to a decreased incidence of treatment-emergent extrapyramidal syndromes (EPS) in patients with schizophrenia was demonstrated in studies conducted in both Japan and Western countries. EPS measurements used in Western countries included the Simpson-Angus, Barnes akathisia and the Abnormal Involuntary Movement Scale, while the Drug-Induced Extrapyramidal Symptom Scale (DIEPSS) was used in Japan. The aim of this study was to clarify how the DIEPSS captures EPS profiles. The baseline prevalence and treatment-emergent incidence of EPS in Japanese schizophrenic patients treated with olanzapine or haloperidol were retrospectively compared as assessed by the DIEPSS to the prevalence and incidence of EPS in primarily Caucasian schizophrenic patients who were treated with olanzapine or haloperidol. Specifically, the prevalence and incidence of dyskinesia, akathisia and parkinsonism were compared between the Japanese trial and an international trial to examine if appropriate definitions using the DIEPSS can be derived assuming that a comparable prevalence and incidence of the syndromes would be observed when any differences in residual antipsychotic exposure at the initiation of study treatment were accounted for. For the incidence of all EPS syndromes, odds ratios were observed to be similar between the two studies, indicating that appropriate criteria for the clinical diagnosis of the EPS syndromes could be established based on the DIEPSS. This preliminary and retrospective work suggests that the DIEPSS can be used to operationally define the presence or absence, and make the clinical diagnosis, of specific EPS syndromes.
Adult↗
Cytochrome P450 II D6 gene polymorphisms and the neuroleptic-induced extrapyramidal symptoms in Japanese schizophrenic patients.
OBJECTIVE: The purpose of this study was to examine whether the neuroleptic-induced extrapyramidal symptoms are associated with the CYP2D6 activity. METHODS: The CYP2D6 gene polymorphisms (CYP2D6*2, CYP2D6*3, CYP2D6*4, CYP2D6*10, and CYP2D6*12) were genotyped in 196 normal controls and 320 schizophrenic patients receiving neuroleptics. The relationships with susceptibility to extrapyramidal symptoms (EPS) and tardive dyskinesia, and with steady-state serum haloperidol levels in maintenance therapy, were investigated. RESULTS: The allele frequency of CYP2D6*2 was significantly higher, while that of CYP2D6*10 tended to be higher in the schizophrenic patients susceptible to acute EPS. The steady-state serum haloperidol levels per daily dosage were observed to be significantly higher in schizophrenic patients with the mutant-type homozygote of CYP2D6*2, while this difference was trend level in those of CYP2D6*10. However, no significant difference was observed in the distribution of both CYP2D6*2 (C2938T) and CYP2D6*10 (C188T) polymorphisms between schizophrenic patients with or without tardive dyskinesia. CONCLUSION: The present results suggest that the homozygotes of CYP2D6*2 and CYP2D6*10 appear to be a susceptibility factor for developing acute EPS in schizophrenic patients and for impaired neuroleptic metabolism in Japanese schizophrenic patients.
Antipsychotic Agents↗
Cytochrome P450 2D6 polymorphism and character traits.
OBJECTIVE: It has been suggested that cytochrome P450 2D6 (CYP2D6) is involved in dopamine metabolism within the brain. The dopamine system is suggested to play a role in determining normal character. The purpose of this study was to examine whether character traits are dependent on cytochrome P450 2D6 activity. METHODS: We investigated the association between temperament and CYP2D6 gene polymorphism. The subjects were all Japanese and the polymorphism genotyped in the present study was CYP2D6*10. Character traits were assessed using the Temperament and Character Inventory. RESULTS: There was no overall or specific association between personality traits and the CYP2D6*10 allele and genotype frequencies. CONCLUSIONS: The present results do not support the hypothesis that CYP2D6 activity affects temperament and character.
Character↗
Extrapyramidal symptom profiles in Japanese patients with schizophrenia treated with olanzapine or haloperidol.
Previous clinical trials have clearly shown the superiority of olanzapine to haloperidol in the improvement of extrapyramidal symptoms (EPS) in schizophrenic patients. The primary purpose of this study was to compare EPS profiles in Japanese schizophrenic patients treated with an atypical antipsychotic, olanzapine, or a typical antipsychotic, haloperidol, as measured by the Drug-Induced Extrapyramidal Symptoms Scale (DIEPSS). The DIEPSS, which consists of eight individual parameters and one global assessment (overall severity), was used to evaluate 182 patients enrolled in this 8-week study. The primary safety analysis was maximum change (that could be either a decrease or increase) from baseline in DIEPSS total score. Secondary analyses included change from baseline to maximum in DIEPSS total score, change from baseline to endpoint (LOCF) in DIEPSS total score, and the rank sum of the maximum change (that could be either a decrease or increase) from baseline in the DIEPSS individual items. Incidence of treatment-emergent EPS adverse events using the DIEPSS scale was also analyzed. The olanzapine group showed statistically significant superiority to the haloperidol group on the primary analysis (p<0.001). Secondary analyses also demonstrated olanzapine's superiority in DIEPSS total, parkinsonism, akathisia and overall severity scores (all p< or =0.014). Categorical analysis of treatment-emergent akathisia and parkinsonism syndromes at endpoint showed improvement in the olanzapine group but worsening in the haloperidol group. The results from this study suggest that olanzapine, as in Caucasian populations, is a safe treatment in Japanese patients chronically ill with schizophrenia.
Adult↗
Nicotine suppresses 1-methyl-4-phenylpyridinium ion-induced hydroxyl radical generation in rat striatum.
The present study examined the ability of antioxidant effects of nicotine on 1-methyl-4-phenylpyridinium ion (MPP(+))-induced hydroxyl radical (*OH) formation of rat striatum. Rats were anesthetized and sodium salicylate in Ringer's solution (0.5 nmol/microl per min) was infused through a microdialysis probe to detect the generation of.OH as reflected by non-enzymatic formation trapped as 2,3-dihydroxybenzoic acid (DHBA) in the striatum. MPP(+) enhanced generation of.OH formation trapped as DHBA. However, nicotine (100 microM) significantly suppressed.OH formation induced by MPP(+). Iron (II) (2, 5 and 10 microM) increased the levels of DHBA in a concentration-dependent manner. However, in the presence of nicotine (100 microM), the effect of nicotine was suppressed. These results suggest that nicotine has a preventive effect on.OH generation by MPP(+) in rat striatum.
1-Methyl-4-phenylpyridinium↗
Are the cochrane group registers comprehensive? A case study of Japanese psychiatry trials.
BACKGROUND: Language bias is a form of publication bias and constitutes a serious threat to meta-analyses. The Cochrane Controlled Trials Register is one attempt to remedy this and now contains more than 300,000 citations. However we are still unsure if it provides comprehensive coverage, particularly for non-English trials. METHODS: We have recently established a comprehensive register of Japanese trials of psychotropic drugs through extensive personal contacts, electronic searches and handsearches. We examined two Cochrane psychiatry group registers against this Japanese database. RESULTS: The Japanese register contained 56 reports of randomized controlled trials (RCTs) of antidepressants for depression but the Cochrane Depression, Anxiety and Neurosis group register contained 18, with an overlap of only nine. The Japanese register contained 61 reports of RCTs of neuroleptics for schizophrenia and the Cochrane Schizophrenia group register contained 36, with an overlap of only six. Taking account of some duplicate publications, only a quarter to a third of all relevant Japanese RCTs were retrievable from the Cochrane group registers. CONCLUSIONS: Similar, or worse, yields may be expected with RCTs conducted in other East Asian countries, and in other fields of medicine. What evidence there is suggests that this situation may lead to a systematic over estimate of treatment effect.
Antidepressive Agents↗
Association between catechol-O-methyltransferase (COMT) polymorphism and severe alcoholic withdrawal symptoms in male Japanese alcoholics.
Catechol-O-methyltransferase (COMT) plays a crucial role in central dopaminergic systems. The allelic association of a functional polymorphism of the COMT gene with the onset, course and clinical characteristics of alcoholism in 91 male Japanese alcoholics and 114 male Japanese controls was examined. There were no statistically significant differences in the frequency of the allele between the alcoholics and the controls. Visual disturbances and auditory disturbances among alcoholic withdrawal symptoms were, however, significantly different among the three groups (p < 0.05). The present results suggest that COMT activity could partially effect the phenotype of alcoholism, especially the appearance of delirium tremens, in these subjects.
Journal Article↗
Association between a polymorphism in the promoter region of the dopamine D2 receptor gene and schizophrenia in Japanese subjects: replication and evaluation for antipsychotic-related features.
To replicate a previously found negative association between the Del allele of the -141C Ins/Del polymorphism in the 5'-promoter region of the dopamine D2 receptor gene (DRD2) and schizophrenia in Japanese subjects and to examine whether this polymorphism is related to the features of antipsychotic drug treatment, we genotyped 94 control subjects and 234 schizophrenic patients. The schizophrenic patients had a significantly lower frequency of the Del allele (p < 0.05). We found a non-significant trend towards a higher frequency of the Del allele in schizophrenic patients susceptible to neuroleptic-induced extrapyramidal symptoms. The daily dosage of haloperidol, the steady-state concentration of serum haloperidol per daily dosage, and the recent 1-yr cumulative neuroleptic dosage were lower in patients with the Del/Del genotype than in the other patients. These findings support the view that the polymorphism is associated with schizophrenia in Japanese subjects and provide hints for further attempts to establish the relationship between this polymorphism and the features of antipsychotic drug treatment.
Journal Article↗